In this program we will investigate the integrated regulation of the airways and blood vessels in the lung. The function of these two systems of distensible tree structures is to allow the passage and distribution of gas and blood, respective. The ability to facilitate these functions is regulated by several factors. First is the fact that, because of the structural nature of the lung, these two systems are in close proximity to each other. This structural proximity leads to a host of mechanical interactions that bear on the regulation of airway and vascular dimensions. Second is the regulation of local function in airways and vessels by respiratory gas concentrations. Third is the innervation of the two systems. Neural reflex control of airways, and pulmonary and bronchial blood vessels by afferent and efferent autonomic nervous system pathways is well documented. In this application we will focus five interrelated projects exploring the mechanisms involved in the functional interactions regulating the airways and blood vessels in the lung. One project focuses on the intrinsic regulation of the vessels, one project focuses on the intrinsic regulation of the airways, two projects deal directly with the physical interactions between vessels and airways, and the last projects deals with a critical component involved in the neural regulation of both the airways and blood vessels of the lung. Although each of these individual projects represents strong and creative research, this program project serves as a vehicle that promotes active collaboration among investigators, opportunities for frequent communication of ideas, and utilization of common resources and facilities. Such interactions provide not only unique opportunities for collaborative research, but also an exciting environment for scholarly activities that have been the long standing focus for the successful training of students and fellows supported by a NHLBI Training Grant. This program project thus provides much more than support for five interrelated projects. In this application we have incorporated new initiatives and methodologies at both the cellular and whole animal level, but a central thrust continues at the systems level. This approach provides a necessary link between rapidly advancing disciplines at the molecular level with real problems experienced in medical and public health settings.